Slc2a5 (Glut5) is essential for the absorption of fructose in the intestine and generation of fructose-induced hypertension.

Abstract

The identity of the transporter responsible for fructose absorption in the intestine in vivo and its potential role in fructose-induced hypertension remain speculative. Here we demonstrate that Glut5 (Slc2a5) deletion reduced fructose absorption by approximately 75% in the jejunum and decreased the concentration of serum fructose by approximately 90% relative to wild-type mice on increased dietary fructose. When fed a control (60% starch) diet, Glut5(-/-) mice had normal blood pressure and displayed normal weight gain. However, whereas Glut5(+/+) mice showed enhanced salt absorption in their jejuna in response to luminal fructose and developed systemic hypertension when fed a high fructose (60% fructose) diet for 14 weeks, Glut5(-/-) mice did not display fructose-stimulated salt absorption in their jejuna, and they experienced a significant impairment of nutrient absorption in their intestine with accompanying hypotension as early as 3-5 days after the start of a high fructose diet. Examination of the intestinal tract of Glut5(-/-) mice fed a high fructose diet revealed massive dilatation of the caecum and colon, consistent with severe malabsorption, along with a unique adaptive up-regulation of ion transporters. In contrast to the malabsorption of fructose, Glut5(-/-) mice did not exhibit an absorption defect when fed a high glucose (60% glucose) diet. We conclude that Glut5 is essential for the absorption of fructose in the intestine and plays a fundamental role in the generation of fructose-induced hypertension. Deletion of Glut5 results in a serious nutrient-absorptive defect and volume depletion only when the animals are fed a high fructose diet and is associated with compensatory adaptive up-regulation of ion-absorbing transporters in the colon.

• Authors: Sharon Barone, Stacey L Fussell, Anurag Kumar Singh, Fred Lucas, Jie Xu, Charles Kim, Xudong Wu, Yiling Yu, Hassane Amlal, Ursula Seidler, Jian Zuo, Manoocher Soleimani
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 284 Issue 8 Pg. 5056-66 (Feb 20 2009) ISSN: 0021-9258 [Print] United States
• PMID: 19091748 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Glucose Transport Proteins, Facilitative
• Glucose Transporter Type 5
• SLC2A5 protein, human
• Slc2a5 protein, mouse
• Sweetening Agents
• Fructose
• Starch
• Glucose

Topics

• Animals
• Blood Pressure (drug effects, genetics)
• COS Cells
• Chlorocebus aethiops
• Diet (adverse effects)
• Fructose (adverse effects, pharmacology)
• Glucose (pharmacology)
• Glucose Transport Proteins, Facilitative (genetics, metabolism)
• Glucose Transporter Type 5 (genetics, metabolism)
• Humans
• Hypertension (chemically induced, genetics, metabolism)
• Intestinal Absorption (drug effects, genetics)
• Intestinal Mucosa (metabolism)
• Ion Transport (drug effects, genetics)
• Mice
• Mice, Knockout
• Starch (pharmacology)
• Sweetening Agents (adverse effects, pharmacology)